Center for Common Disease Genetics

项目摘要 基于我们在全面基因组研究和解决 NHGRI的目标，这RFA，我们建议创建，应用和测试一个强大的，可靠的， “全面”识别风险和保护性变体的一般策略， 对任何常见疾病都有显著影响。为此，我们将： ·创建一个共同疾病联盟（CDC），汇集一个协作网络 研究人员具有深厚的临床和遗传专业知识， 不同人群的样本（病例和对照），包括欧洲人、非洲人、 美国人，西班牙人和亚洲人。疾病预防控制中心将在三个主要领域进行遗传研究。 相关项目：（1）五种全身性疾病-早发性冠状动脉疾病，2型 糖尿病、炎症性肠病、心房颤动和中风;（2）三种严重的 神经系统疾病-自闭症、精神分裂症和癫痫;以及（3）两个国家有特殊的 遗传学研究的优势-芬兰和爱沙尼亚。通过这三个项目，CDC 将探索一系列的研究设计，群体遗传策略，遗传结构， 不同的人群。 ·利用布罗德研究所的专业知识，对来自CDC的45万个样本进行测序。 基因组学平台，以生成高质量的数据，并降低测序成本。 ·分析序列数据以阐明疾病的遗传基础，通过应用状态- 最先进的方法，从我们的初步研究和开发新的方法，以增加 检测关联的能力。 ·创建、传播和共享数据、工具和资源，以使科学 社区访问和分析来自CDC和其他来源的遗传研究。

Project Summary Abstract Building on our 25-year track record in comprehensive genomic studies and addressing NHGRI's goal for this RFA, we propose to create, apply and test a powerful, reliable and general strategy for “comprehensive” identification of risk and protective variants that contribute significantly to any common disease of interest. Toward this end, we will: · Create a Common Disease Consortium (CDC) that brings together a collaborative network of investigators with deep clinical and genetic expertise and >1.1 million well-characterized samples (cases and controls) across diverse populations, including Europeans, African Americans, Hispanics and Asians. The CDC will undertake genetic studies under three major projects related to: (1) Five systemic diseases – early-onset coronary artery disease, type 2 diabetes, inflammatory bowel disease, atrial fibrillation, and stroke; (2) Three severe neurological disorders – autism, schizophrenia and epilepsy; and (3) Two countries with special advantages for genetic studies – Finland and Estonia. Through these three projects, the CDC will explore a range of study designs, population-genetic strategies, genetic architectures, and diverse populations. · Sequence 450,000 samples from the CDC, using the expertise of the Broad Institute's genomics platform to generate high quality data and to drive down sequencing costs. · Analyze the sequence data to elucidate the genetic basis of the diseases, by applying state- of-the-art methods from in our preliminary studies and developing new methods to increase power to detect association. · Create, disseminate and share data, tools, and resources, to enable the scientific community to access and analyze genetic studies from the CDC and other sources.